Use of Substituted 2-Pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-A] Pyrimidin-4-one and 7-Pyrimidinyl-2,3-dihydroimidazo[1,2-A] Pyrimidin-5(1H)one Derivatives

ABSTRACT

The invention relates to use of a pyrimidone derivative represented by formula (I) or a salt thereof as therapeutic agents: 
     
       
         
         
             
             
         
       
     
     Wherein m, n, p, X, Y, R1, R2, R3, R4 R5, are as defined herein. The invention specifically relates to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease.

This application is a continuation of U.S. application Ser. No.10/490,136, filed Aug. 11, 2004, now allowed, which was the NationalStage of International application No. PCT/EP02/11,127, filed Sep. 19,2002; both of which are incorporated herein by reference in theirentirety; which claims the benefit of priority of European PatentApplication No. 01402431.9, filed Sep. 21, 2001 and European PatentApplication No. 02290488.2, filed Feb. 28, 2002.

TECHNICAL FIELD

The present invention relates to compounds that are useful as an activeingredient of a medicament for preventive and/or therapeutic treatmentof neurodegenerative diseases caused by abnormal activities of GSK3βalone or by the combined effects of GSK3β and cdk5/p25.

BACKGROUND ART

GSK3β (glycogen synthase kinase 3β) is a proline directed serine,threonine kinase that plays an important role in the control ofmetabolism, differentiation and survival. It was initially identified asan enzyme able to phosphorylate and hence inhibit glycogen synthase. Itwas later recognized that GSK3β was identical to tau protein kinase 1(TPK1), an enzyme that phosphorylates tau protein in epitopes that arealso found to be hyperphosphorylated in Alzheimer's disease and inseveral taupathies.

Interestingly, protein kinase B (AKT) phosphorylation of GSK3β resultsin a loss of its kinase activity, and it has been hypothesized that thisinhibition may mediate some of the effects of neurotrophic factors.Moreover, phosphorylation by GSK3β of β-catenin, a protein involved incell survival, results in its degradation by an ubiquitinilationdependent proteasome pathway.

Thus, it appears that inhibition of GSK3β activity may result inneurotrophic activity. Indeed there is evidence that lithium, anon-competitive inhibitor of GSK3β, enhances neuritogenesis in somemodels and also increases neuronal survival, through the induction ofsurvival factors such as Bcl-2 and the inhibition of the expression ofproapoptotic factors such as P53 and Bax.

Recent studies have demonstrated that β-amyloid increases the GSK3βactivity and tau protein phosphorylation. Moreover, thishyperphosphorylation as well as the neurotoxic effects of β-amyloid areblocked by lithium chloride and by a GSK3β antisense mRNA. Theseobservations strongly suggest that GSK3β may be the link between the twomajor pathological processes in Alzheimer's disease: abnormal APP(Amyloid Precursor Protein) processing and tau proteinhyperphosphorylation.

Although tau hyperphosphorylation results in a destabilization of theneuronal cytoskeleton, the pathological consequences of abnormal GSK3βactivity are, most likely, not only due to a pathologicalphosphorylation of tau protein because, as mentioned above, an excessiveactivity of this kinase may affect survival through the modulation ofthe expression of apoptotic and antiapoptotic factors. Moreover, it hasbeen shown that β-amyloid-induced increase in GSK3β activity results inthe phosphorylation and, hence the inhibition of pyruvate dehydrogenase,a pivotal enzyme in energy production and acetylcholine synthesis.

Cdk5/p25, also known as tau protein kinase 2 (TPK2), is a prolinedirected, Ser/Thr kinase essential for central nervous systemdevelopment and in particular for neuronal migration and neuriteoutgrowth. Cdk5 is a homologue of cyclin-dependent kinases and ratherubiquitously expressed. Its activator p35 (a 305 aa protein) or atruncated form p25 (208 aa, missing an N-terminal proline-rich domainnot required for activity) are selectively expressed in neurons,limiting cdk5 kinase activity essentially to the CNS. Cdk5 is completelyinactive in the absence of p35 or p25. The term cdk5/p25 will be usedhere for the active enzyme since evidence exists suggesting that p25 andless so p35 may be involved in pathological processes.

Physiological substrates of cdk5/p25 include DARPP-32, Munc-18, PAK1,synapsin 1 and perhaps some others. In addition, it is now wellestablished that cdk5/p25 phosphorylates tau protein epitopes which arehyperphosphorylated in Alzheimer's disease. More recently, elevatedcdk5/p25 activity, mislocalization of cdk5 and an increase in p25activator has been found in the brain of Alzheimer patients.Interestingly, prephosphorylation of tau protein by cdk5/p25considerably enhances phosphorylation of tau by GSK3β on other epitopes,also found hyperphosphorylated in Alzheimer's disease. Moreover,neurofibrillary tangles, the hallmark of Alzheimer's disease, arelabeled with antisera for GSK3β and cdk5, but not GSK3α and MAP kinase,also, GSK3β and cdk5 are associated with microtubules and both, morethan PKA and CK, contribute to the AD-like phosphorylation of tauprotein. These results taken together suggest that mixed inhibitors ofGSK3β and cdk5/p25 should efficient in protecting tau protein fromhyperphosphorylation. Therefore, they would be useful in the treatmentof any pathological disorder associated with the abnormalphosphorylation of tau protein, in particular Alzheimer's disease, butalso other taupathies (e.g. frontotemporoparietal dementia, corticobasaldegeneration, Pick's disease, progressive supranuclear palsy).

Cdk5/p25 has been linked to apoptosis and neurodegeneration in moregeneral terms. Its overexpression induces apoptosis in cultured neurons,in brain tissue apoptotic cells show strong immunoreactivity for cdk5.Neurotoxic agents, incl. Aβ(1-42), neuronal injury, ischemia or growthfactor withdrawal lead to activation and mislocalization of cdk5/p25,abnormal phosphorylation of cdk5 substrates, cytoskeletal disruption andcell death. Moreover, phosphorylation by cdk5/p25 transforms DARPP-32into an inhibitor of protein kinase A, reducing signal transduction inthe striatum with obvious implications for Parkinson's disease. A rolefor cdk5 in ALS has also been proposed based on its ability tophosphorylate neurofilaments. More recently, deregulation of cdk5 wasdetected in a mouse model of amyotrophic lateral sclerosis.

Altogether, these experimental observations indicate that GSK3βinhibitors may find application in the treatment of theneuropathological consequences and the cognitive and attention deficitsassociated with Alzheimer's disease, as well as other acute and chronicneurodegenerative diseases. These include, in a non-limiting manner,Parkinson's disease, taupathies (e.g. frontotemporoparietal dementia,corticobasal degeneration, Pick's disease, progressive supranuclearpalsy) and other dementia including vascular dementia; acute stroke andothers traumatic injuries; cerebrovascular accidents (e.g. age relatedmacular degeneration); brain and spinal cord trauma; peripheralneuropathies; retinopathies and glaucoma. In addition GSK3β inhibitionmay find application in the treatment of other diseases such as:

Non-insulin dependent diabetes (such as diabetes type II) and obesity;manic depressive illness; schizophrenia; alopecia; cancers such asbreast cancer, non-small cell lung carcinoma, thyroid cancer, T orB-cell leukemia and several virus-induced tumors.

Since it appears that both, GSK3β and cdk5/p25 play a major role in theinduction of apoptosis in neuronal cells, combined inhibition of thesetwo enzymes may find application in the treatment of not onlyAlzheimer's disease and the other above-mentioned taupathies, but alsoin a number of other neurodegenerative disorders, in particularParkinson's disease and amyotrophic lateral sclerosis; other dementiasincluding vascular dementia; acute stroke and other traumatic injuries;cerebrovascular accidents (e.g. age related macular degeneration); brainand spinal cord trauma; peripheral neuropathies; retinopathies andglaucoma.

In addition mixed TPK1/TPK2 inhibitors may find their applications inthe treatment of other diseases such as: smoking cessation and otherwithdrawal syndromes, epilepsy.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide compounds useful as anactive ingredient of a medicament for preventive and/or therapeutictreatment of a disease caused by abnormal GSK3β or GSK3β and cdk5/p25activity, more particularly of neurodegenerative diseases. Morespecifically, the object is to provide novel compounds useful as anactive ingredient of a medicament that enables prevention and/ortreatment of neurodegenerative diseases such as Alzheimer's disease.

Thus, the inventors of the present invention have identified compoundspossessing inhibitory activity against GSK3β or GSK3β and cdk5/p25. As aresult, they found that compounds represented by the following formula(I) had the desired activity and were useful as an active ingredient ofa medicament for preventive and/or therapeutic treatment of theaforementioned diseases.

The present invention thus provides pyrimidone derivatives representedby formula (I) or salts thereof, solvates thereof or hydrates thereof:

wherein:

X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C₁₋₂alkyl group and a hydrogen atom;Y represents a bond, an ethenylene group, an ethynylene group, an oxygenatom, a sulfur atom, a sulfonyl group, a sulfoxide group, a carbonylgroup, a nitrogen atom being optionally substituted by a C₁₋₆ alkylgroup, a phenyl or a benzyl group; or a methylene group optionallysubstituted by one or two groups chosen from a C₁₋₆ alkyl group, abenzyl group, a hydroxyl group, a C₁₋₄ alkoxy group, a C₃₋₆cycloalkylmethyloxy, a C₁₋₂ perhalogenated alkyl group, an amino group,an acetylamino group or a phenyl group;R1 represents a pyrimidine ring optionally substituted by a C₃₋₆cycloalkyl group a C₁₋₄ alkyl group, a C₁₋₄ alkoxy group, a benzyl groupor a halogen atom;

when Y represents a bond, a methylene group optionally substituted or acarbonyl group then R2 represents a C₁₋₆ alkyl group optionallysubstituted by a C_(6,10) aryloxy or a C_(6,10) arylamino group; a C₃₋₆cycloalkyl group, a C₁₋₄ alkylthio group, a C₁₋₄ alkoxy group, a C₁₋₂perhalogenated alkyl group, a C₁₋₃ halogenated alkyl group, a phenylthiogroup, a benzyl group, a benzene ring, an indan ring, a5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring,a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; thebenzyl group or the rings being optionally substituted by 1 to 4substituents selected from a C₁₋₆ alkyl group, a methylenedioxy group, ahalogen atom, a C₁₋₂ perhalogenated alkyl group, a C₁₋₃ halogenatedalkyl group, a hydroxyl group, a C₁₋₄ alkoxy group, a nitro, a cyano, anamino, a C₁₋₅ monoalkylamino group, a C₂₋₁₀ dialkylamino group, a C₁₋₆alkylcarbonylamino group, a C_(6,10) arylcarbonylamino group, a C₁₋₄alkylsulfonyl group, C₁₋₄ alkylsulfonyloxy group or a phenyl group;

when Y represents an ethenylene group, an ethynylene group, an oxygenatom, a sulfur atom, a sulfonyl group, a sulfoxide group or a nitrogenatom being optionally substituted then R2 represents a C₁₋₆ alkyl group(optionally substituted by a C_(6,10) aryloxy or a C_(6,10) arylaminogroup), a C₃₋₆ cycloalkyl group, a C₁₋₂ perhalogenated alkyl group, aC₁₋₃ halogenated alkyl group, a benzyl group, a benzene ring, an indanring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, apyridine ring, a pyrrole ring, a thiophene ring, a furan ring or animidazole ring; the benzyl group or the rings being optionallysubstituted by 1 to 4 substituents selected from a C₁₋₆ alkyl group, amethylenedioxy group, a halogen atom, a C₁₋₂ perhalogenated alkyl group,a C₁₋₃ halogenated alkyl group, a hydroxyl group, a C₁₋₄ alkoxy group, anitro, a cyano, an amino, a C₁₋₅ monoalkylamino group, a C₂₋₁₀dialkylamino group, a C₁₋₆ alkylcarbonylamino group, a C_(6,10)arylcarbonylamino group, a C₁₋₄ alkylsulfonyl group, C₁₋₄alkylsulfonyloxy group or a phenyl group;

R3 and R4 represent each independently a hydrogen atom, C₁₋₆ alkylgroup, a hydroxy group, a C₁₋₄ alkoxy group or a halogen atom;R5 represents a hydrogen atom, a C₁₋₆ alkyl group or a halogen atom;When m equals 0, p equals 1, 2 or 3,When m equals 1, p equals 0, 1 or 2,When m equals 2, p equals 0 or 1;and n represents 0 to 3.

According to another aspect of the present invention, there is provideda medicament comprising as an active ingredient a substance selectedfrom the group consisting of the pyrimidone derivatives represented byformula (I) and the physiologically acceptable salts thereof, and thesolvates thereof and the hydrates thereof. As preferred embodiments ofthe medicament, there are provided the aforementioned medicament whichis used for preventive and/or therapeutic treatment of diseases causedby abnormal GSK3β or GSK3β and cdk5/p25 activity, and the aforementionedmedicament which is used for preventive and/or therapeutic treatment ofneurodegenerative diseases and in addition other diseases such as:

Non-insulin dependent diabetes (such as diabetes type II) and obesity;manic depressive illness; schizophrenia; alopecia; smoking cessation andother withdrawal syndromes, epilepsy; cancers such as breast cancer,non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia andseveral virus-induced tumors.

As further preferred embodiments of the present invention, there areprovided the aforementioned medicament wherein the diseases areneurodegenerative diseases and are selected from the group consisting ofAlzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis,taupathies (e.g. frontotemporoparietal dementia, corticobasaldegeneration, Pick's disease, progressive supranuclear palsy) and otherdementia including vascular dementia; acute stroke and others traumaticinjuries; cerebrovascular accidents (e.g. age related maculardegeneration); brain and spinal cord trauma; peripheral neuropathies;retinopathies and glaucoma, and the aforementioned medicament in theform of pharmaceutical composition containing the above substance as anactive ingredient together with one or more pharmaceutical additives.

The present invention further provides an inhibitor of GSK3β or GSK3βand cdk5/p25 activity comprising as an active ingredient a substanceselected from the group consisting of the pyrimidone derivatives offormula (I) and the salts thereof, and the solvates thereof and thehydrates thereof.

According to further aspects of the present invention, there is provideda method for preventive and/or therapeutic treatment ofneurodegenerative diseases caused by abnormal GSK3β or GSK3β andcdk5/p25 activity, which comprises the step of administering to apatient a preventively and/or therapeutically effective amount of asubstance selected from the group consisting of the pyrimidonederivatives of formula (I) and the physiologically acceptable saltsthereof, and the solvates thereof and the hydrates thereof; and a use ofa substance selected from the group consisting of the pyrimidonederivatives of formula (I) and the physiologically acceptable saltsthereof, and the solvates thereof and the hydrates thereof for themanufacture of the aforementioned medicament.

As used herein, the C₁₋₆ alkyl group represents a straight or branchedalkyl group having 1 to 6 carbon atoms, for example, methyl group, ethylgroup, n-propyl group, isopropyl group, n-butyl group, isobutyl group,sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group,neopentyl group, 1,1-dimethylpropyl group, n-hexyl group, isohexylgroup, and the like;

The ethenylene group represents the divalent group of formula:

The ethynylene group represents the divalent group of formula:

The C₁₋₄ alkoxy group represents an alkyloxy group having 1 to 4 carbonatoms for example, methoxy group, ethoxy group, propoxy group,isopropoxy group, butoxy group, isobutoxy group, sec-butoxy group,tert-butoxy group, and the like;

The halogen atom represents a fluorine, chlorine, bromine or iodineatom;

The C₁₋₂ perhalogenated alkyl group represents an alkyl group whereinall the hydrogen have been substituted by a halogen atom, for example aCF₃ or C₂F₅;

The C₁₋₃ halogenated alkyl group represents an alkyl group wherein atleast one hydrogen has not been substituted by a halogen atom;

The C₁₋₅ monoalkylamino group represents an amino group substituted byone C₁₋₅ alkyl group, for example, methylamino group, ethylamino group,propylamino group, isopropylamino group, butylamino group, isobutylaminogroup, tert-butylamino group, pentylamino group and isopentylaminogroup;

The C₂₋₁₀ dialkylamino group represents an amino group substituted bytwo C₁₋₅ alkyl groups, for example, dimethylamino group,ethylmethylamino group, diethylamino group, methylpropylamino group anddiisopropylamino group;

The C₆₋₁₀ arylamino represents a phenylamino group or naphthylaminogroup; a C₆₋₁₀ aryloxy represents a phenyloxy group or naphthyloxygroup.

The leaving group represents a group which could be easily cleaved andsubstituted, such a group may be for example a tosyloxy, a mesyloxy, abromide and the like.

The compounds represented by the aforementioned formula (I) may form asalt. Examples of the salt include, when an acidic group exists, saltsof alkali metals and alkaline earth metals such as lithium, sodium,potassium, magnesium, and calcium; salts of ammonia and amines such asmethylamine, dimethylamine, trimethylamine, dicyclohexylamine,tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine,2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, andL-glucamine; or salts with basic amino acids such as lysine,6-hydroxylysine, and arginine. The base-addition salts of acidiccompounds are prepared by standard procedures well known in the art.

When a basic group exists, examples include salts with mineral acidssuch as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid; salts with organic acids such as methanesulfonic acid,benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propionicacid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid,succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid,lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinicacid, and salicylic acid; or salts with acidic amino acids such asaspartic acid, and glutamic acid.

The acid-addition salts of the basic compounds are prepared by standardprocedures well know in the art which include, but are not limitedthereto, dissolving the free base in an aqueous alcohol solutioncontaining the appropriate acid and isolating the salt by evaporatingthe solution, or by reacting the free base and an acid in an organicsolvent, in which case the salt separates directly, or is precipitatedwith a second organic solvent, or can be obtained by concentration ofthe solution. The acids which can be used to prepare the acid-additionsalts include preferably those which produce, when combined with thefree base, pharmaceutically-acceptable salts, that is, salts whoseanions are relatively innocuous to the animal organism in pharmaceuticaldoses of the salts, so that the beneficial properties inherent in thefree base are not compromised by side effects ascribable to the anions.Although medicinally acceptable salts of the basic compounds arepreferred, all acid-addition salts are within the scope of the presentinvention.

In addition to the pyrimidone derivatives represented by theaforementioned formula (I) and salts thereof, their solvates andhydrates also fall within the scope of the present invention. Thepyrimidone derivatives represented by the aforementioned formula (I) mayhave one or more asymmetric carbon atoms. As for the stereochemistry ofsuch asymmetric carbon atoms, they may independently be in either (R)and (S) configuration, and the pyrimidone derivative may exist asstereoisomers such as optical isomers, or diastereoisomers. Anystereoisomers in pure form, any mixtures of stereoisomers, racemates andthe like fall within the scope of the present invention.

Examples of preferred compounds of the present invention are shown intable 1 hereinafter. However, the scope of the present invention is notlimited by these compounds.

Preferred compounds of the present invention represented by formula (I)include also:

-   (1) Compounds wherein R1 represents a 4- or 5-pyrimidine ring and    more preferably 4-pyrimidine ring, which may be substituted by a    C₁₋₂ alkyl group, a C₁₋₂ alkoxy group or a halogen atom; and/or-   (2) X represents hydrogen atoms or a C₁₋₂ alkyl group and a hydrogen    atom;-   (3) Y represents a carbonyl group or a methylene group optionally    substituted by one or two groups chosen from a C₁₋₆ alkyl group, a    benzyl group, a hydroxyl group, a C₁₋₄ alkoxy group, a C₃₋₆    cycloalkylmethyloxy; and/or-   (4) When m equals 0, p equals 1 or 2; and/or-   (5) R2 represents a benzene ring, an indan ring, a    5,6,7,8-tetrahydronaphthalene ring a naphthalene ring or a    cyclohexyl ring.

More preferred compounds of the present invention represented by formula(I) include also:

(1) Compounds wherein R1 represents an unsubstituted 4-pyrimidine ringand compounds wherein R1 represents an unsubstituted 4-pyrimidine ringand X, Y and R2 are as defined for the preferred compounds.Particularly preferred compounds of the present invention represented byformula (I) include compounds of table 1:

-   1.    9-(3-Phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   2.    9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl])-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   3.    9-(2-Phenylsulfanyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   4.    9-(2-Oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   5.    9-(3-Hydroxy-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   6.    9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   7.    9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   8.    9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   9.    9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   10.    9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   11.    9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   12.    9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   13.    9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   14.    9-(1-Methyl-2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   15.    9-(2-Hydroxy-1-methyl-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   16.    9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   17.    7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   18.    7,7-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   19.    9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   20.    9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   21.    9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   22.    9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   23.    3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   24.    3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   25.    9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   26.    9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   27.    9-[2-Oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,tetrahydro-naphthalen-2-yl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   28.    9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   29.    9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   30.    9-(2-Naphthalen-2-yl-2-oxo-ethy)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   31.    9-(2-Oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   32.    9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   33.    9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   34.    9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   35.    9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   36.    9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   37.    7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,-tetrahydro-naphthalen-2-yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   38.    9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-7,7,-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   39.    9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   40.    7,7-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   41.    9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   42.    7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   43.    9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   44.    9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   45.    9-(2-Hydroxy-2-phenyl-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   46.    9-[2-(2-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   47.    9-[2-(2-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   48.    9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   49.    9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   50.    9-[2-(2,5-Dimethoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   51.    9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   52.    9-[2-(2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   53.    9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   54.    9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   55.    9-[2-Ethoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   56.    9-[2-Hydroxy-2-(2-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   57.    9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   58.    9-(2-(Benzo-[1,3]dioxol-5-yl)-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   59.    9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   60.    9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   61.    9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   62.    9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   63.    9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   64.    4-[2-(3,3-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4,dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)ethyl]benzonitrile-   65.    9-[2-(4-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   66.    9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   67.    7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   68.    7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   69.    9-[2-(4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   70.    9-[2-(4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   71.    9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   72.    9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   73.    9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   74.    9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   75.    9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   76.    9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   77.    9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   78.    9-[2-(2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   79.    9-[2-(3-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   80.    9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   81.    7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   82.    9-[2-(3-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   83.    9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   84.    9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   85.    9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   86.    9-[2-(4-Fluoro-2-methoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   87.    7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   88.    9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   89.    9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   90.    9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   91.    9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   92.    9-[2-(2,6-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   93.    7,7-Dimethyl-9-(2-naphthalen-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   94.    9-[2-(2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   95.    7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2-trifluoromethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   96.    9-[2-(2,4-Dichloro-5-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   97.    7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   98.    9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   99.    9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   100.    3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   101.    9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   102.    9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   103.    9-[2-(4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   104.    9-[2-(5-Chloro-2,3-dihydro-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one    and compounds of table 2:-   1.    1-(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   2.    1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   3.    1-(2-Oxo-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   4.    1-(2-Hydroxy-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   5.    1-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   6.    1-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   7.    1-(2-Biphenyl-4-yl-2-oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   8.    1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   9.    2,2-Dimethyl-1-(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   10.    2,2-Dimethyl-1-(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   11.    1-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one-   12.    2,2-Dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)ethyl]-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;    and compounds of table 3-   1.    9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   2.    9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   3.    9-[2-(4-Fluoro-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   4.    8-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   5.    9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one.-   6.    9-[2-(2-Methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   7.    9-[2(S)-Hydroxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   8.    9-[2(R)-Methoxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   9.    9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   10.    8-Methyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   11.    9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   12.    8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   13.    9-[2(R)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   14.    9-[2-(4-Fluoro-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   15.    8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   16.    9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   17.    9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   18.    8,8-Dimethyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   19.    8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   20.    9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   21.    8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   22.    9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   23.    9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   24.    9-[2-(2,4-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   25.    9-[2-(3-Bromo-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   26.    9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   27.    9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   28.    9-[2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   29.    9-[2-(3-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   30.    9-(2(S)-Hydroxy-2-naphthalen-2-yl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   31.    9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   32.    9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   33.    9(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   34.    9-[2(S)-Hydroxy-2-(3-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   35.    9-[2-(4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   36.    9-[2-(2,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   37.    3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   38.    8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   39.    9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one-   40.    9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   41.    4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)-[(S)-hydroxy-ethyl]-benzonitrile;-   42.    9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   43.    9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   44.    9-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   45.    8,8-Dimethyl-9-(2-naphtalen-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   46.    9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   47.    9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   48.    9-(2-Biphenyl-4-yl-2-oxo-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   49.    9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   50.    9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   51.    8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   52.    9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;-   53.    9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl]8-ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one.

As a further object, the present invention concerns also methods forpreparing the compounds represented by the aforementioned formula (I).

These compounds can be prepared, for example, according to methodsexplained below.

Preparation Method

Pyrimidone compounds represented by the aforementioned formula (I) maybe prepared according to scheme 1.

(In the above scheme the definition of R1, R2, R3, R4, R5, X, p, m and nare the same as those already described for compound of formula (I)).

The pyrimidin-5(1H)-one derivative represented by the above formula(III), wherein R1 is as defined for compound of formula (I), is allowedto react with a base such as sodium hydride, sodium carbonate orpotassium carbonate in a solvent such as N,N-dimethylformamide,N-methylpyrrolidine, N,N-dimethylacetamide or chloroform at a suitabletemperature ranging from 0 to 130° C. under ordinary air, then with acompound of formula (II), wherein R2, X, Y and n are as defined forcompound of formula (I) and L represents a leaving group preferablybromide or mesyloxy group, is added to obtain the compound of theaforementioned formula (I).

Compound of formula (II) are commercially available or may besynthesized according to well-known methods of one skilled in the art.The compound of formula (III) may be prepared according to the methoddefined in scheme 2.

(In the above scheme the definition of R1, R3, R4, R5, p and m are thesame as already described.)

According to this method, the 3-ketoester of formula (IV) is allowed toreact with a compound of formula (V). The reaction may be carried out inthe presence of potassium carbonate, in an alcoholic solvent such asmethanol, ethanol and the like or without, at a suitable temperatureranging from 25°-140° C. under ordinary air.

Alternatively, compounds of formula (III) wherein R5 represents ahydrogen atom may be halogenated in order to give compounds of formula(III) wherein R5 is a halogen atom such as a bromine atom or a chlorineatom.

The reaction may be carried out in an acidic medium such as acetic acidor propionic acid, in presence of bromosuccinimide or chlorosuccinimide,or bromine.

In addition, compounds of formula (III) wherein R5 represents a fluorineatom may be obtained by analogy to the method described in TetrahedronLetters, Vol. 30, N^(o) 45, pp 6113-6116, 1989.

Compounds of formula (V) or (IV) are commercially available or may besynthesized according to well-known methods of one skilled in the art.

For example compounds of formula (IV), wherein R1 represent a pyrimidinering optionally substituted by a C₁₋₄ alkyl group, C₁₋₄ alkoxy group ora halogen atom, can be prepared by reacting a pyrimidine-4-carboxylicacid optionally substituted by a C₁₋₄ alkyl group, C₁₋₄ alkoxy group ora halogen, with a malonic acid monoester. The reaction can be carriedout using methods well known to one skilled in the art, such as forexample in presence of a coupling agent such as1,1′-carbonylbis-1H-imidazole in a solvent such as tetrahydrofuran at atemperature ranging from 20 to 70° C.

Compounds of formula (I) may also be obtained starting from anothercompound of formula (I) using well-known methods of one skilled in theart.

In the above reactions, protection or deprotection of a functional groupmay sometimes be necessary. A suitable protecting group Pg can be chosendepending on the type of the functional group, and a method described inthe literature may be applied. Examples of protecting groups, ofprotection and deprotection methods are given for example in Protectivegroups in Organic Synthesis Greene et al., 2nd Ed. (John Wiley & Sons,Inc., New York).

The compounds of the present invention have inhibitory activity againstGSK3β or GSK3β and cdk5/p25. Accordingly, the compounds of the presentinvention are useful as an active ingredient for the preparation of amedicament, which enables preventive and/or therapeutic treatment of adisease caused by abnormal GSK3β or GSK3β and cdk5/p25 activity and moreparticularly of neurodegenerative diseases such as Alzheimer's disease.In addition, the compounds of the present invention are also useful asan active ingredient for the preparation of a medicament for preventiveand/or therapeutic treatment of neurodegenerative diseases such asParkinson's disease, amyotrophic lateral sclerosis, taupathies (e.g.frontotemporoparietal dementia, corticobasal degeneration, Pick'sdisease, progressive supranuclear palsy) and other dementia includingvascular dementia; acute stroke and others traumatic injuries;cerebrovascular accidents (e.g. age related macular degeneration); brainand spinal cord trauma; peripheral neuropathies; retinopathies andglaucoma; and other diseases such as non-insulin dependent diabetes(such as diabetes type II) and obesity; manic depressive illness;schizophrenia; alopecia; smoking cessation and other withdrawalsyndromes, epilepsy; cancers such as breast cancer, non-small cell lungcarcinoma, thyroid cancer, T or B-cell leukemia and severalvirus-induced tumors.

The present invention further relates to a method for treatingneurodegenerative diseases caused by abnormal activity of GSK3β or GSK3βand cdk5/p25 and of the aforementioned diseases which comprisesadministering to a mammalian organism in need thereof an effectiveamount of a compound of the formula (I).

As the active ingredient of the medicament of the present invention, asubstance may be used which is selected from the group consisting of thecompound represented by the aforementioned formula (I) andpharmacologically acceptable salts thereof, and solvates thereof andhydrates thereof. The substance, per se, may be administered as themedicament of the present invention, however, it is desirable toadminister the medicament in a form of a pharmaceutical compositionwhich comprises the aforementioned substance as an active ingredient andone or more pharmaceutical additives. As the active ingredient of themedicament of the present invention, two or more of the aforementionedsubstances may be used in combination. The above pharmaceuticalcomposition may be supplemented with an active ingredient of anothermedicament for the treatment of the above mentioned diseases. The typeof pharmaceutical composition is not particularly limited, and thecomposition may be provided as any formulation for oral or parenteraladministration. For example, the pharmaceutical composition may beformulated, for example, in the form of pharmaceutical compositions fororal administration such as granules, fine granules, powders, hardcapsules, soft capsules, syrups, emulsions, suspensions, solutions andthe like, or in the form of pharmaceutical compositions for parenteraladministrations such as injections for intravenous, intramuscular, orsubcutaneous administration, drip infusions, transdermal preparations,transmucosal preparations, nasal drops, inhalants, suppositories and thelike. Injections or drip infusions may be prepared as powderypreparations such as in the form of lyophilized preparations, and may beused by dissolving just before use in an appropriate aqueous medium suchas physiological saline. Sustained-release preparations such as thosecoated with a polymer may be directly administered intracerebrally.

Types of pharmaceutical additives used for the manufacture of thepharmaceutical composition, content ratios of the pharmaceuticaladditives relative to the active ingredient, and methods for preparingthe pharmaceutical composition may be appropriately chosen by thoseskilled in the art. Inorganic or organic substances, or solid or liquidsubstances may be used as pharmaceutical additives. Generally, thepharmaceutical additives may be incorporated in a ratio ranging from 1%by weight to 90% by weight based on the weight of an active ingredient.

Examples of excipients used for the preparation of solid pharmaceuticalcompositions include, for example, lactose, sucrose, starch, talc,cellulose, dextrin, kaolin, calcium carbonate and the like. For thepreparation of liquid compositions for oral administration, aconventional inert diluent such as water or a vegetable oil may be used.The liquid composition may contain, in addition to the inert diluent,auxiliaries such as moistening agents, suspension aids, sweeteners,aromatics, colorants, and preservatives. The liquid composition may befilled in capsules made of an absorbable material such as gelatin.Examples of solvents or suspension mediums used for the preparation ofcompositions for parenteral administration, e.g. injections,suppositories, include water, propylene glycol, polyethylene glycol,benzyl alcohol, ethyl oleate, lecithin and the like. Examples of basematerials used for suppositories include, for example, cacao butter,emulsified cacao butter, lauric lipid, witepsol.

The dose and frequency of administration of the medicament of thepresent invention are not particularly limited, and they may beappropriately chosen depending on conditions such as a purpose ofpreventive and/or therapeutic treatment, a type of a disease, the bodyweight or age of a patient, severity of a disease and the like.Generally, a daily dose for oral administration to an adult may be 0.01to 1,000 mg (the weight of an active ingredient), and the dose may beadministered once a day or several times a day as divided portions, oronce in several days. When the medicament is used as an injection,administrations may preferably be performed continuously orintermittently in a daily dose of 0.001 to 100 mg (the weight of anactive ingredient) to an adult.

CHEMICAL EXAMPLES

The present invention will be explained more specifically with referenceto the following general examples, however, the scope of the presentinvention is not limited to these examples.

Example 1 (Compound No. 24 of Table 1)3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one1.12-(Pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

A mixture of 1.75 g (9.0 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the methoddescribed in patent DE 2705582), 5.0 g (30.55 mmol)1,4,5,6-tetrahydro-2-pyrimidinamine dihydrochloride (prepared by analogyto U.S. Pat. No. 4,262,122) and 2.49 g (18.0 mmol) of potassiumcarbonate in 30 ml of methanol were heated at reflux temperature during18 h.

The reaction mixture was cooled and the solvent removed by evaporation.The residue obtained was treated with water and the precipitaterecovered by filtration to give 1.15 g (56%) of product. Mp.: 268-272°C.

1.23-Chloro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

A suspension of 3.0 g (13.09 mmol) of2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-onein 60 ml of acetic acid was treated with 1.75 g (15.7 mmol) ofN-chlorosuccinimide. The reaction mixture was heated at 90° C. during 18h.

The cooled solution was evaporated to remove the solvent and water wasadded. The product was recovered, rinsed with diethylether and dried togive 2.95 g (86%) of solid. Mp.: 208-210° C.

1.33-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.6 g (2.27 mmol) of3-chloro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-onein 6.7 ml of anhydrous dimethylformamide was added 0.20 g (5.10 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture allowedto stir at 50° C. for 20 min. 0.361 ml (2.73 mmol) of(S)-2-chloro-1-phenylethanol was added and stirring continued for 18 h.

Water was added and the mixture extracted with dichloromethane. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 96/4 gave 0.598 g(69%) of pure product. Mp.: 158-160° C.

Example 2 (Compound No. 23 in Table 1)3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one2.13-Methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

A mixture of 10.72 g (51.48 mmol) of ethyl3-(4-pyrimidinyl)-2-methyl-3-oxopropionate, (prepared by analogy to themethod described in patent DE 2705641 and U.S. Pat. No. 4,110,450) 6.98g (51.48 mmol) of 1,4,5,6-tetrahydro-2-pyrimidinamine dihydrochloride

(prepared by analogy to U.S. Pat. No. 4,262,122) and 7.11 g (51.48 mmol)of potassium carbonate in 250 ml of ethanol were heated at refluxtemperature during 5 h.

The reaction mixture was cooled and the solvent removed by evaporation.The residue obtained was treated with water and the precipitaterecovered by filtration. The filtrate was dissolved in chloroform andthe solution filtered and evaporated to give 8.6 g (69%) of product.Mp.: 206-207° C.

2.23-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

A solution containing 0.608 g (2.5 mmol) of3-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-onein anhydrous dimethylformamide was treated with 0.11 g (2.5 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture warmed to40° C. during 1 h. 0.497 g (2.5 mmol) of phenacyl bromide dissolved in 5ml of dimethylformamide was added dropwise and the resulting solutionstirred at room temperature for 3 h. The reaction mixture was treatedwith a saturated aqueous solution of sodium chloride and then extractedwith ethyl acetate. The organic extracts were dried and evaporated togive a crude product, which was purified by chromatography on silica geleluting with dichloromethane/methanol/ammonia in the proportions 100/0/0to 98/2/0.2. A pure product was obtained which was triturated indiethylether to give 0.309 g (34%) of yellow solid. Mp.: 184-185° C.

Example 3 (Compound No. 17 in Table 1)7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one3.1 5,5-Difluoro-1,4,5,6-tetrahydro-2-pyrimidinamine

A mixture of 2.95 g (16.12 mmol) of 2,2-difluoro-1,3-propandiaminedihydrochloride (Tetrahedron (1994) 50(29), 8617-8632), 1.54 g (16.12mmol) of guanidine hydrochloride and 2.19 g (32.23 mmol) of sodiummethylate was heated at 150° C. during 18 h. The cooled mixture was usedas such in the subsequent step.

3.27,7-Difluoro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

To a suspension of 2.17 g (16.12 mmol) of5,5-difluoro-1,4,5,6-tetrahydro-2-pyrimidinamine and 1.81 g (16.12 g) ofpotassium carbonate in 30 ml of ethanol was treated with 2.55 g (13.13mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate. The reaction mixturewas heated at reflux temperature during 32 h.

The cooled reaction mixture was evaporated and the resulting residuetreated with water and extracted with dichloromethane. The extracts weredried and evaporated and the residue was purified by chromatography onsilica gel eluting with a mixture of dichloromethane/methanol/ammonia inthe proportions 97.5/2.5/0.25. 0.22 g (6.3%) of product was thusobtained.

3.37,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

A solution of 0.22 g (0.829 mmol) of7,7-difluoro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-onein 4 ml of anhydrous dimethylformamide was treated with 36.2 mg (0.829mmol) of sodium hydride (60% suspension in mineral oil) and the mixturewarmed to 40° C. during 30 min. The cooled solution (−10° C.) wastreated with 0.165 g (0.829 mmol) of phenacyl bromide and the resultingmixture stirred at room temperature for 1 h.

Water was added and the reaction mixture extracted with ethyl acetate.The extracts were dried and evaporated to leave a residue which waspurified by chromatography on silica gel eluting with a mixture ofdichloromethane/methanol/ammonia in the proportions 98/2/0.2 to give 56mg (17%) of product. Mp.: 233-234° C.

Example 4 (Compound No. 19 in Table 1)9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one4.17,7-Dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

A mixture containing 5.15 g (26.52 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the methoddescribed in patent DE 2705582), 4.34 g (26.52 mmol) of5,5-dimethyl-1,4,5,6-tetrahydro-2-pyrimidinamine monohydrochloride(prepared by analogy to U.S. Pat. No. 4,262,122) and 3.66 g (26.5 mmol)of potassium carbonate in 60 ml of methanol were heated at refluxtemperature during 18 h.

The cooled reaction mixture was evaporated and water was added. Theresulting precipitate was recovered by filtration and dried to give 4.86g (71%) of product. Mp.: 194-196° C.

4.29-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.40 g (1.55 mmol) of7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 10 ml of anhydrousdimethylformamide was added 0.132 g (3.42 mmol) of sodium hydride (60%suspension in mineral oil) and the resulting mixture stirred for 15 min.at room temperature. 0.535 g (3.42 mmol) of (S)-2-chloro-1-phenylethanolwas added and the reaction mixture was heated at 50° C. for 7 h.

The cooled reaction mixture was treated with water and extracted withethyl acetate. The extracts were dried and evaporated and the residueobtained was purified by chromatography on silica gel eluting with amixture of dichloromethane/methanol in the proportions 100/0 to 95/5 togive 0.084 g (14%) of product which was transformed into thehydrochloride salt in the usual manner. Mp.: 113-115° C. [∀]_(D)+54.7°(c=0.6, CH₃OH).

Example 5 (Compound No. 54 in Table 1)9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.092 g (0.244 mmol) of7,7-dimethyl-9-[2-(2(S)-hydroxy-phenyl-ethyl)]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-onein 3 ml of anhydrous dimethylformamide was added 0.010 g (0.244 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture stirredat room temperature during 1 h. To this solution cooled to 0° C. wasadded 0.019 ml (0.244 mmol) of iodoethane and the mixture heated at 60°C. during 2 h. Water was added and the mixture extracted withdichloromethane. The extracts were washed with a saturated aqueoussolution of sodium chloride and dried and evaporated. The residue waspurified by chromatography on silica gel eluting with a mixture ofdichloromethane/methanol/ammonia in the proportions 95/5/0.5 to give 57mg (56%) of product. Mp.: 113-115° C. [∀]_(D)+19.4° (c=0.82, CH₃OH).

Example 6 (Compound No. 58 in Table 1)9-(2-Benzo[1,3]dioxol-5-yl-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one6.17,7-Dimethyl-9-(2-oxo-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 3.815 g (14.83 mmol) of7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 50 ml of anhydrous dimethylformamide was added 0.771 g (19.28 mmol)of sodium hydride (60% suspension in mineral oil). The suspension wasstirred at room temperature for 30 min. at room temperature. 1.54 ml(19.28 mmol) of 1-chloropropanone was added and the solution was heatedat 60° C. during 4 h.

Water was added to the cooled solution and the mixture extracted withdichloromethane. The extracts were washed with a saturated aqueoussolution of sodium chloride and dried and evaporated. The residue waspurified by chromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 90/10 to give 2.58g (85%) of product.

6.29-(2-Benzo[1,3]dioxol-5-yl-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.3 g (0.957 mmol) of7,7-dimethyl-9-(2-oxo-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 2 ml of anhydrous tetrahydrofuran at −2° C. was added 2.1 ml (9.57mmol) of a solution of 3,4-(methylenedioxy)phenylmagnesiumbromide (1Msolution in tetrahydrofuran/toluene 50/50) during 20 min. After stirringfor 15 min. at room temperature the reaction was quenched by theaddition of a saturated aqueous solution of ammonium chloride. Thereaction mixture was extracted with dichloromethane and the extractswashed with a saturated aqueous solution of sodium chloride, dried andevaporated. The residue was purified by chromatography on silica geleluting with a mixture of ethyl acetate/cyclohexane in the proportions50/50 to 100/0 to give 0.210 g (50%) of product. Mp.: 194-196° C.

Example 7 (Compound No. 2 in Table 2)1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-onehydrochloride (1:1) 7.1 5,5-Dimethyl-4,5-dihydro-1H-imidazol-2-ylaminehydrobromide (1:1)

To a solution of 15 g (0.17 mol) of 1,2-diamino-2-methylpropane in 150ml of water at 0° C., was added 18 g (0.17 mol) of cyanogen bromideportionwise and the temperature was allowed to warm to room temperatureduring 4 h.

The water was removed by evaporation and ethanol was added andevaporated. Trituration in a mixture of diethyl ether and ethanol gave29.5 g (89%) of product as an amorphous hygroscopic solid.

7.22,2-Dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one

A mixture containing 2.0 g (10.3 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, 2.0 g (10.3 mmol) of5,5-dimethyl-4,5-dihydro-1H-imidazol-2-ylamine hydrobromide and 2.85 g(20.6 mmol) of potassium carbonate in 15 ml of methanol were heated atreflux temperature during 18 h.

The solvent was removed by evaporation and the residue was treated withwater and extracted with dichloromethane. The extracts were dried andevaporated to give 0.960 g (39%) of product. Mp.: 238-240° C.

7.31-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-onehydrochloride (1:1)

A solution of 0.2 g (0.822 mmol) of2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-onein 6 ml of anhydrous dimethylformamide was treated with 39 mg (0.986mmol) of sodium hydride (60% suspension in mineral oil) and the mixtureheated at 60° C. for 10 min. To the cooled reaction mixture was added0.210 g (0.904 mmol) of 1-[3-(methylsulfonyloxy)propyl]-2-fluorobenzeneand heating maintained at 130° C. for 1 h.

Water was added and the reaction mixture was extracted with ethylacetate. The combined extracts were washed with a saturated aqueoussolution of sodium chloride, dried and evaporated. The residue obtainedwas purified by chromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 99/1 to 90/10 to give 0.25 g(80%) of product which was treated with one equivalent of hydrogenchloride in isopropanol to give the monohydrochloride. Mp.: 170-172° C.

Example 8 (Compound No. 1 in Table 3)9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one8.18-Methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

A mixture of 7.76 g (40.0 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the methoddescribed in patent DE 2705582), 6.0 g (40.0 mmol)6-methyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrochloride

(prepared according to J. Org. Chem., 20, 1955, 829-838) and 8.29 g(60.0 mmol) of potassium carbonate in 50 ml of ethanol were heated atreflux temperature during 18 h.

The reaction mixture was cooled and the solvent removed by evaporation.The residue obtained was treated with water and the precipitaterecovered by filtration to give 3.81 g (39%) of product. Mp.: 199-201°C.

8.2 (4-Fluoro-2-methoxy-phenyl)-acetic acid methyl ester

To a suspension of 14.34 g (32.47 mmol) of lead (IV) acetate in 100 mlof anhydrous toluene was added a mixture of 5.2 g (30.92 mmol) of1-(4-fluoro-2-methoxy-phenyl)-ethanone and 15.02 ml (123.13 mmol) ofboron trifluoride etherate in 9 ml of methanol. The reaction mixture isfurther stirred at room temperature for 16 h. Water was added to thecooled mixture and the resulting solution extracted with toluene. Theextracts were washed with saturated sodium hydrogen carbonate solution,saturated sodium chloride solution and dried with sodium sulfate. Thesolvent was evaporated to dryness to give 6 g of product as an oil,which was used in the subsequent step without further purification.

8.3 2-(4-Fluoro-2-methoxy-phenyl)-ethanol

To a suspension of 1.72 g (45.41 mmol) of lithium aluminum hydride in120 ml of tetrahydrofuran at 0° C. was added dropwise 6 g (30.27 mmol)of dissolved in 120 ml of (4-Fluoro-2-methoxy-phenyl)-acetic acid methylester and the resulting mixture stirred at room temperature for 1 h.

The reaction mixture was diluted with 100 ml of diethylether at 0° C.and treated with excess of a saturated aqueous solution of sodiumsulfate. Further solid sodium sulfate was added and the organic phasewas filtered to remove salts. The solvent was evaporated to dryness togive 5.1 g (99%) of product as an oil.

8.4 Methanesulfonic acid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester

To a solution of 5.1 g (29.97 mmol) of2-(4-Fluoro-2-methoxy-phenyl)-ethanol in 30 ml of anhydrousdichloromethane was added at 0° C. 6.26 ml (44.95 mmol) of triethylamineand 3.5 ml (44.95 mmol) of methanesulfonyl chloride.

The resulting mixture was stirred at 0° C. for 1 h. The mixture was thendiluted with water and dichloromethane and extracted withdichloromethane.

Organic layer was dried and evaporated to give 7 g (100%) ofmethanesulfonic acid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester.

8.59-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.18 g (0.74 mmol) of8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 4 ml of anhydrous dimethylformamide was added 0.033 g (0.81 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture allowedto stir at 50° C. for 20 min. 0.202 g (0.81 mmol) of methanesulfonicacid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester was added and stirringcontinued for 18 h.

Water was added and the mixture extracted with dichloromethane. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 96/4 gave 0.154 g(53%) of pure product. Mp.: 148-150° C.

Example 9 (Compound No. 2 in Table 3)9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one9.18,8-Dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

A mixture of 2.39 g (12.31 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the methoddescribed in patent DE 2705582), 2.33 g (11.19 mmol)6,6-dimethyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrobromide

(prepared according to Bull. Soc. Chim. Belg., 1950, 59, 573-587) and3.25 g (23.5 mmol) of potassium carbonate in 25 ml of ethanol wereheated at reflux temperature during 18 h.

The reaction mixture was cooled and the solvent removed by evaporation.The residue obtained was treated with water and the precipitaterecovered by filtration to give 1 g (35%) of product. Mp.: 265-267° C.

9.29-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.2 g (0.78 mmol) of8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 5 ml of anhydrous dimethylformamide was added 0.035 g (0.86 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture allowedto stir at 50° C. for 20 min. 0.212 g (0.86 mmol) of methanesulfonicacid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester was added and stirringcontinued for 18 h.

Water was added and the mixture extracted with dichloromethane. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 96/4 gave 0.136 g(43%) of pure product. Mp.: 196-198° C.

Example 10 (Compound No. 11 in Table 3)9-(2(S)-Hydroxy-2-phenyl-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.2 g (0.78 mmol) of8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 3 ml of anhydrous dimethylformamide was added 0.07 g (1.71 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture wasallowed to stir at 50° C. for 1 h. 0.158 g (1.01 mmol) of(1-S)-2-chloro-1-phenyl ethanol was added and the mixture allowed tostir at 120° C. for 12 h.

Water was added and the mixture extracted with ethyl acetate. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 96/24 gave 0.21 g(72%) of pure product. Mp.: 178-179° C., [∀]_(D)=+45.7° (c=0.784,CHCl₃).

Example 11 (Compound No. 15 in Table 3)8,8-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.24 ml (3.3 mmol) of dimethyl sulfoxide in 3 ml ofanhydrous dichloromethane at −780° C. was added 0.42 ml (2.93 mmol) oftrifluoroacetic anhydride in 2 ml of anhydrous dichloromethane and themixture allowed to stir at −78° C. for 20 min. 0.201 g (0.53 mmol) of9-(2(S)-Hydroxy-2-phenyl-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 2 ml of anhydrous dichloromethane was added at −78° C. and stirringcontinued for 30 min. 0.62 ml (4.47 mmol) of triethylamine was added andthe mixture allowed to stir at room temperature for 12 h. Water wasadded and the mixture extracted with ethyl acetate, the extracts werewashed with a saturated aqueous solution of ammonium chloride, asaturated aqueous solution of sodium chloride, dried and evaporated togive crude product. Purification by chromatography on silica gel elutingwith ethyl acetate gave 0.045 g (23%) of pure product. Mp.: 203-205° C.

Example 12 (Compound No. 19 in Table 3)8-Ethyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one12.18-Ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

A mixture of 5 g (25.75 mmol) of ethyl3-(4-pyrimidinyl)-3-oxopropionate, 3.83 g (23.41 mmol) of6-ethyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrochloride (preparedaccording to J. Org. Chem., 20, 1955, 829-838) and 6.794 g (49.16 mmol)of potassium carbonate in 50 ml of ethanol were heated at refluxtemperature during 18 h.

The reaction mixture was cooled and the solvent removed by evaporation.The residue obtained was treated with water and the precipitaterecovered by filtration to give 3.62 g (60%) of product. Mp.: 226-228°C.

12.28-Ethyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.35 g (1.36 mmol) of8-ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 7 ml of anhydrous dimethylformamide was added 0.071 g (1.77 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture allowedto stir at 25° C. for 15 min. At 0° C., 0.352 g (1.77 mmol) of phenacylbromide was added. The mixture was allowed to stir at 0° C. for 3 h andthe temperature was allowed to warm to room temperature during 12 h.

Water was added and the mixture extracted with ethyl acetate. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with a mixture ofdichloromethane/methanol in the proportions 100/0 to 98/2 gave 0.163 g(32%) of pure product. Mp: 187-189° C.

Example 13 (Compound No. 20 in Table 3)9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one13.1 (1S)-2-Bromo-1-phenyl-ethanol

To a solution of 2.30 ml (2.30 mmol) of borane tetrahydrofuran complex(1 M solution in tetrahydrofuran) was added at −30° C. 0.46 ml (0.46mmol) of (S)-2-methyl-CBS-oxazaborolidine (1M solution in toluene). 0.5g (2.30 mmol) of 4′-Fluoro-phenacyl bromide in 1.85 ml of anhydrousdichloromethane was added to the solution over 1 hour while the internaltemperature was maintained at −30° C. The mixture was stirred at −20° C.for 1 hour. 1.85 ml of methanol was added to the reaction mixture. Thesolution was warmed to room temperature, 5.55 ml of aqueous hydrochloricacid (1N) was added. The mixture extracted with ethyl acetate, theextracts were dried over sodium sulfate and concentrated in vacuo togive 0.498 g of 2-Bromo-1-phenyl-ethanol, which was used withoutpurification in the next reaction.

13.29-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one

To a solution of 0.3 g (1.17 mmol) of8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-onein 5 ml of anhydrous dimethylformamide was added 0.105 g (2.57 mmol) ofsodium hydride (60% suspension in mineral oil) and the mixture allowedto stir at 50° C. for 1 h. 0.332 g (1.01 mmol) of (1-S)-2-bromo-1-phenylethanol was added and the mixture allowed to stir at 120° C. for 12 h.

Water was added and the mixture extracted with ethyl acetate. Theextracts were washed with a saturated aqueous solution of sodiumchloride, dried and evaporated to give crude product. Purification bychromatography on silica gel eluting with ethyl acetate gave 0.24 g(52%) of pure product. Mp.: 176-178° C., [∀]_(D)=+51.6° (c=0.844,CHCl₃).

A list of chemical structures and physical data for compounds of theaforementioned formula (I) illustrating the present invention is givenin tables 1, 2 and 3. The compounds have been prepared according to themethods of the example.

In the tables, R1 is an unsubstituted pyrimidin-4-yl group, Phrepresents a phenyl group, Et represents an ethyl group, Me represents amethyl group, (S), (R) or (Rac.) indicates in the column “Y” thestereochemistry of the carbon atom.

(rac.) means racemic mixture(R) means absolute R configuration(S) means absolute S configuration

In table 1 for compounds of formula (I) “m” and “p” equal 1; in table 2for compounds of formula (I) “m” equals 0 and p equals 1 and in table 3for compounds of formula (I) “m” equals 0 and “p” equals 2.

TABLE 1

No. X Y R5 R2 R3 R4 n Mp ° C. salt 1 H CH₂ H Ph H H 1 148-152 (1:1hydro- chloride 2 H CH₂ H

H H 0 226-228 (1:1) hydro-chloride 3 H S H Ph H H 1 160-162 (1:1) hydro-chloride 4 H CO H Ph H H 0 200-202 (1:1) hydro- chloride 5 H CH(OH) H PhH H 1 103-105 (1:1) hydro- (rac.) chloride 6 H CH(OH) H Ph H H 0 174-176Free base (rac.) 7 H CO H Ph H H 1 180-182 (1:1) hydro- chloride 8 HCH(OH) H Ph H H 0 152-154 Free base (R) 9 H CH(OH) H Ph H H 0 151-153Free base (S) 10 H CO H

H H 0 181-183 (1:1) hydro-chloride 11 H CO H

H H 0 211-213 (1:1) hydro-chloride 12 H CH(OH)(rac.) H

H H 0 160-162 Free base 13 H CH(OH)(rac.) H

H H 0 188-190 (1;1) hydro-chloride 14 H, CH₃ CO H Ph H H 0 170-172 Freebase (rac.) 15 H, CH₃ CH(OH) H Ph H H 0 241-244 Free base (rac.) (rac.)16 H CH(OH)(R) H

H H 0 142-144 (1:1) hydro-chloride 17 H CO H Ph F F 0 233-235 Free base18 H CO H Ph CH₃ CH₃ 0 232-234 (1:1) hydro- chloride 19 H CH(OH) H PhCH₃ CH₃ 0 113-115 (1:1) hydro- (S) chloride 20 H CO H

CH₃ CH₃ 0 178-180 (1:1) hydro-chloride 21 H CH(OH)(rac.) H

CH₃ CH₃ 0 157-159 Free base 22 H CO H

CH₃ CH₃ 0 215-217 Free base 23 H CO CH₃ Ph H H 0 184-185 Free base 24 HCH(OH) Cl Ph H H 0 158-160 Free base (S) 25 H CH(OH) CH₃ Ph H H 0175-176 Free base (S) 26 H CH(OH)(rac.) H

CH₃ CH₃ 0 183-184 Free Base 27 H CO H

H H 0 215 Free Base 28 H CO H

H H 0 233-234 Free base 29 H CO H

H H 0 200-201 Free base 30 H CO H

H H 0 218-219 Free base 31 H CO H

H H 0 211-212 Free base 32 H CO H

H H 0 253-254 Free base 33 H CO H

H H 0 185-186 Free base 34 H, CH₃(rac.) CO H

H H 0 51-52 Free base 35 H, CH₃(rac.) CO H

CH₃ CH₃ 0 199-200 Free base 36 H CO H

CH₃ CH₃ 0 222-223 Free base 37 H CO H

CH₃ CH₃ 0 214-215 Free base 38 H CO H

CH₃ CH₃ 0 220-221 Free base 39 H CO H

CH₃ CH₃ 0 225-226 Free base 40 H CO H

CH₃ CH₃ 0 223-224 Free base 41 H CO H

CH₃ CH₃ 0 166-167 Free base 42 H CO H

CH₃ CH₃ 0 210-211 Free base 43 H, CH₃(rac.) CH(OH)(rac.) H

CH₃ CH₃ 0 216-217 Free base 44 H, CH₃(rac.) CH(OH)(rac.) H

H H 0 247 Free base 45 H C(OH)(CH₃) H Ph CH₃ CH₃ 0 182-184 Free base(rac.) 46 H CO H

CH₃ CH₃ 0 215-217 Free base 47 H CH₂ H

CH₃ CH₃ 0 148-150 Free base 48 H CH(OH)(rac.) H

CH₃ CH₃ 0 190-192 Free base 49 H CO H

CH₃ CH₃ 0 152-154 Free base 50 H CH(OH)(rac.) H

CH₃ CH₃ 0 190-192 Free base 51 H

H Ph CH₃ CH₃ 0 118-120 Free base 52 H CH(OEt)(rac.) H

CH₃ CH₃ 0 142-144 Free base 53 H CH(OH)(rac.) H

CH₃ CH₃ 0 186-188 Free base 54 H CH(OEt) H Ph CH₃ CH₃ 0 113-115 Freebase (S) 55 H CH(OEt)(rac.) H

CH₃ CH₃ 0 170-172 Free base 56 H C(OH)(CH₃)(rac.) H

CH₃ CH₃ 0 178-180 Free base 57 H CH₂ H

CH₃ CH₃ 0 188-190 Free base 58 H C(OH)(CH₃)(rac.) H

CH₃ CH₃ 0 194-196 Free base 59 H C(OH)(CH₃)(rac.) H

CH₃ CH₃ 0 144-146 Free base 60 H C(OH)(CH₃)(rac.) H

CH₃ CH₃ 0 187-189 Free base 61 H CH₂ H

CH₃ CH₃ 0 191-193 Free base 62 H CH₂ H

CH₃ CH₃ 0 159-161 Free base 63 H CH₂ H

CH₃ CH₃ 0 162-164 Free base 64 H CH₂ H

CH₃ CH₃ 0 197-199 Free base 65 H CH₂ H

CH₃ CH₃ 0 149-151 Free base 66 H CH₂ H

CH₃ CH₃ 0 147-149 Free base 67 H CH₂ H

CH₃ CH₃ 0 157-159 Free base 68 H CH₂ H

CH₃ CH₃ 0 150-151 Free base 69 H CH(OH)(rac.) H

CH₃ CH₃ 0 170-172 Free base 70 H CO H

CH₃ CH₃ 0 246-248 Free base 71 H CH₂ H

CH₃ CH₃ 0 201-203 Free base 72 H CH₂ H

CH₃ CH₃ 0 169-171 Free base 73 H CH₂ H

CH₃ CH₃ 0 181-183 Free base 74 H CH₂ H

CH₃ CH₃ 0 194-196 Free base 75 H CH₂ H

CH₃ CH₃ 0 137-139 Free base 76 H CH₂ H

CH₃ CH₃ 0 180-182 Free base 77 H CH₂ H

CH₃ CH₃ 0 234-236 Free base 78 H CH₂ H

CH₃ CH₃ 0 180-182 Free base 79 H CH₂ H

CH₃ CH₃ 0 143-145 Free base 80 H CH₂ H

CH₃ CH₃ 0 161-163 Free base 81 H CH₂ H

CH₃ CH₃ 0 172-174 Free base 82 H CH₂ H

CH₃ CH₃ 0 136-138 Free base 83 H CH(OMe)(Rac.) H

CH₃ CH₃ 0 165-167 Free base 84 H CH(OMe)(R) H Ph CH₃ CH₃ 0 110-112 Freebase 85 H CH(OMe)(Rac.) H

CH₃ CH₃ 0 181-182 Free base 86 H CH(OMe)(Rac.) H

CH₃ CH₃ 0 190-192 Free base 87 H CH₂ H Ph CH₃ CH₃ 0 138-140 Free base 88H CH(OMe)(Rac.) H

CH₃ CH₃ 0 160-161 Free base 89 H CH(OMe)(Rac.) H

CH₃ CH₃ 0 169-170 Free base 90 H CH₂ H

CH₃ CH₃ 0 162-164 Free base 91 H CH₂ H

H H 0 170-172 Free base 92 H CH₂ H

CH₃ CH₃ 0 202-204 Free base 93 H CH₂ H

CH₃ CH₃ 0 145-147 Free base 94 H CH₂ H

CH₃ CH₃ 0 170-172 Free base 95 H CH₂ H

CH₃ CH₃ 0 114-116 Free base 96 H CH₂ H

CH₃ CH₃ 0 198-200 Free base 97 H CH₂ H

CH₃ CH₃ 0 230-232 Free base 98 H CH₂ H

CH₃ CH₃ 0 185-187 Free base 99 H bond H

CH₃ CH₃ 0 186-188 Free base 100 H bond Cl

CH₃ CH₃ 0 177-179 Free base 101 H CH₂ H

CH₃ CH₃ 0 126-128 Free base 102 H CH₂ H

CH₃ CH₃ 0 116-118 Free base 103 H CH₂ H

CH₃ CH₃ 0 230-232 Free base 104 H CH₂ H

CH₃ CH₃ 0 206-208 Free base

TABLE 2

No. X Y R5 R2 R3 R4 n Mp °C. salt 1 H CH₂ H Ph H H 1 122-126 (1:1)hydro-chloride 2 H CH₂ H

CH₃ CH₃ 1 170-172 (1:1) hydro-chloride 3 H CO H Ph H H 0 214-216 (1:1)hydro-chloride 4 H CH(OH) H Ph H H 0 184-186 Free base (rac.) 5 H CO H

CH₃ CH₃ 0 168-169 Free base 6 H, CH₃(rac.) CO H

CH₃ CH₃ 0 178-179 Free base 7 H CO H

CH₃ CH₃ 0 223-224 Free base 8 H CO H

CH₃ CH₃ 0 186-187 Free base 9 H CO H

CH₃ CH₃ 0 168 Free base 10 H CO H

CH₃ CH₃ 0 172-173 Free base 11 H CO H

CH₃ CH₃ 0 186 Free base 12 H CO H

CH₃ CH₃ 0 216-217 Free base

TABLE 3

N° X Y R2 R3 R4 R5 n Mp ° C. salt 1 H CH₂

CH₃(Rac.) H H 0 148-150 Free base 2 H CH₂

CH₃ CH₃ H 0 196-198 Free base 3 H CH₂

CH₃(Rac.) H H 0 138-140 Free base 4 H CO Ph CH₃ H H 0 184-186 Free base(Rac.) 5 H CH₂

CH₃(Rac.) H H 0 154-156 Free base 6 H CH₂

CH₃(Rac.) H H 0 127-129 Free base 7 H C(H)(OH) Ph CH₃ H H 0 162-164 Freebase (S) (Rac.) 8 H C(H)(OMe) Ph CH₃ H H 0 181-183 Free base (R) (Rac.)9 H CH₂

CH₃ CH₃ H 0 192-194 Free base 10 H Bond

CH₃(Rac.) H H 0 133-135 Free base 11 H C(H)(OH) Ph CH₃ CH₃ H 0 178-180Free base (S) 12 H Bond

CH₃(Rac.) H H 0  95-97 Free base 13 H C(H)(OH) Ph CH₃ CH₃ H 0 181-183Free base (R) 14 H CH₂

CH₃ CH₃ H 0 182-184 Free base 15 H CO Ph CH₃ CH₃ H 0 203-205 Free base16 H CO

CH₃(Rac.) H H 0 149-151 Free base 17 H CO

CH₃(Rac.) H H 0 169-171 Free base 18 H Bond

CH₃ CH₃ H 0 201-203 Free base 19 H CO Ph Et H H 0 187-189 Free base(Rac.) 20 H C(H)(OH)(S)

CH₃ CH₃ H 0 176-178 Free base 21 H C(H)(OH) Ph Et H H 0 129-131(1:1)Hydro- (S) (Rac.) chloride 22 H C(H)(OH)(S)

CH₃ CH₃ H 0 142-144 Free base 23 H C(H)(OH)(Rac.)

CH₃(Rac.) H H 0 144-146 (1:1)Hydro-chloride 24 H C(H)(OH)(S)

CH₃ CH₃ H 0 139-141 Free base 25 H C(H)(OH)(S)

CH₃ CH₃ H 0 189-191 Free base 26 H CO

CH₃(Rac.) H H 0 241-243 Free base 27 H CO

CH₃(Rac.) H H 0 244-246 Free base 28 H C(H)(OH)(Rac.)

CH₃(Rac.) H H 0 195-197 (1:1)Hydro-chloride 29 H C(H)(OH)(S)

CH₃ CH₃ H 0 177-179 Free base 30 H C(H)(OH)(S)

CH₃ CH₃ H 0 182-184 Free base 31 H C(H)(OH)(S)

CH₃ CH₃ H 0 202-204 Free base 32 H C(H)(OH)(S)

CH₃ CH₃ H 0 206-208 Free base 33 H C(H)(OH)(S)

CH₃ CH₃ H 0 164-166 Free base 34 H C(H)(OH)(S)

CH₃ CH₃ H 0 165-167 Free base 35 H C(H)(OH)(S)

CH₃ CH₃ H 0 170-172 Free base 36 H C(H)(OH)(S)

CH₃ CH₃ H 0 219-221 Free base 37 H CO Ph CH₃ H Br 0 190-192 Free base(rac.) 38 H CO

CH₃ CH₃ H 0 174-176 Free base 39 H C(H)(OH)(S)

CH₃ CH₃ H 0 201-203 Free base 40 H CO

CH₃ CH₃ H 0 162-164 Free base 41 H C(H)(OH)(S)

CH₃ CH₃ H 0 177-179 Free base 42 H CO

CH₃ CH₃ H 0 211-213 Free base 43 H CO

CH₃ CH₃ H 0 209-211 Free base 44 H CO

CH₃ CH₃ H 0 214-216 Free base 45 H CO

CH₃ CH₃ H 0 211-213 Free base 46 H CO

CH₃ CH₃ H 0 188-190 Free base 47 H CO

CH₃ CH₃ H 0 147-149 Free base 48 H CO

CH₃ CH₃ H 0 243-245 Free base 49 H CO

CH₃ CH₃ H 0 157-159 Free base 50 H CO

CH₃ CH₃ H 0 196-198 Free base 51 H C(H)(OH)(S)

Et(Rac) H H 0  95-97 Free base 52 H CO

Et(Rac) H H 0 183-185 Free base 53 H C(H)(OH)(S)

Et(Rac) H H 0 160-162 Free base

Test Example 1 Inhibitory Activity of the Medicament of the PresentInvention Against GSK3β

Two different protocols can be used.

In a first protocol: 7.5 μM of prephosphorylated GS1 peptide and 10 μMATP (containing 300,000 cpm of 33P-ATP) were incubated in 25 mMTris-HCl, pH 7.5, 0.6 mM DTT, 6 mM MgCl₂, 0.6 mM EGTA, 0.05 mg/ml BSAbuffer for 1 hour at room temperature in the presence of GSK3β (totalreaction volume: 100 microliters).

In a second protocol: 4.1 μM of prephosphorylated GS1 peptide and 42 μMATP (containing 260,000 cpm 33P-ATP) were incubated in 80 mM Mes-NaOH,pH 6.5, 1 mM Mg acetate, 0.5 mM EGTA, 5 mM 2-mercaptoethanol, 0.02%Tween 20, 10% glycerol buffer for 2 hours at room temperature in thepresence of GSK3β.

Inhibitors were solubilized in DMSO (final solvent concentration in thereaction medium, 1%).

The reaction was stopped with 100 microliters of a solution made of 25 gpolyphosphoric acid (85% P₂O₅), 126 ml 85% H₃PO₄, H₂O to 500 ml and thendiluted to 1:100 before use. An aliquot of the reaction mixture was thentransferred to Whatman P81 cation exchange filters and rinsed with thesolution described above. Incorporated 33P radioactivity was determinedby liquid scintillation spectrometry.

The phosphorylated GS-1 peptide had the following sequenceNH2-YRRAAVPPSPSLSRHSSPHQS(P)EDEE-COOH.

The GSK3β inhibitory activity of the compounds of the present inventionare expressed in IC₅₀, and as an illustration the range of IC₅₀'s of thecompounds in table 1 is between 2 nanomolar to 2 micromolarconcentrations, of the compounds in table 2 is between 30 nanomolar to 2micromolar concentrations and of the compounds in table 3 is between 1nanomolar to 2 micromolar concentrations.

Test Example 2 Inhibitory Activity of the Medicament of the PresentInvention Against cdk5/p25

The following protocol may be used:

0.4 mg/ml Histone H1 and 10 μM ATP (containing 300,000 cpm of ³³P-ATP)were incubated in 50 mM Hepes, pH 7.2, 1 mM DTT, 1 mM MgCl₂, 1 mM EGTA,0.02% Tween 20 buffer for 1 hour at room temperature in the presence ofcdk5/p25 (total reaction volume: 100 microliters).

Inhibitors were solubilized in DMSO (final solvent concentration in thereaction medium, 1%).

The reaction was stopped with 100 microliters of a solution of 25 gpolyphosphoric acid (85% P₂O₅), 126 ml 85% H₃PO₄, H₂O to 500 ml (dilutedto 1:100 before use). An aliquot of the reaction mixture was thentransferred to Whatman P81 cation exchange filters and rinsed with thesolution described above. Incorporated ³³P radioactivity was determinedby liquid scintillation spectrometry.

The cdk5/p25 inhibitory activity of the compounds of the presentinvention are expressed as IC₅₀ values. Typically, 3-fold serialdilutions of the inhibitor over at least a 1000-fold concentration rangeare used.

As an illustration the range of IC₅₀'s of the compounds in table 1 isbetween 200 nanomolar to 5 micromolar concentrations, of the compoundsin table 2 is between 100 nanomolar to 5 micromolar concentrations andof the compounds in table 3 is between 100 nanomolar to 5 micromolarconcentrations.

As an illustration the specific IC₅₀'s of some compounds of theaforementioned formula (I) illustrating the present invention are givenin table 4.

TABLE 4 Table No. Compound No. TPK1 IC50 μM TPK2 IC50 μM 3 35 0.002 >1.03 11 0.004 1.177 3 7 0.012 0.833 1 91 0.0035 >1.0 1 69 0.004 >1.0 1 470.005 >1.0 1 19 0.008 0.377 1 9 0.002 0.49 1 24 >0.10 0.833 1 23 0.0320.754

Formulation Example (1) Tablets

The ingredients below were mixed by an ordinary method and compressed byusing a conventional apparatus.

Compound of Example 1 30 mg Crystalline cellulose 60 mg Corn starch 100mg Lactose 200 mg Magnesium stearate 4 mg

(2) Soft Capsules

The ingredients below were mixed by an ordinary method and filled insoft capsules.

Compound of Example 1 30 mg Olive oil 300 mg Lecithin 20 mg

(1) Parenteral Preparations

The ingredients below were mixed by an ordinary method to prepareinjections contained in a 1 ml ampoule.

Compound of Example 1 3 mg Sodium chloride 4 mg Distilled water forinjection 1 ml

INDUSTRIAL APPLICABILITY

The compounds of the present invention have GSK3β or GSK3β and cdk5/p25inhibitory activity and are useful as an active ingredient of amedicament for preventive and/or therapeutic treatment of diseasescaused by abnormal activity of GSK3β or GSK3β and cdk5/p25 and moreparticularly of neurodegenerative diseases.

Although the invention has been illustrated by certain of the precedingexamples, it is not to be construed as being limited thereby; butrather, the invention encompasses the generic area as hereinbeforedisclosed. Various modifications and embodiments can be made withoutdeparting from the spirit and scope thereof.

1. A method for the treatment of a disease selected from the groupconsisting of Alzheimer's disease and taupathies, which comprisesadministering to a patient in need of said treatment an effective amountof a compound of formula (I) or a pharmaceutically acceptable saltthereof:

wherein: X represents two hydrogen atoms, a sulfur atom, an oxygen atomor a C₁₋₂ alkyl group and a hydrogen atom; Y represents a covalentsingle bond, an ethenylene group, an ethynylene group, an oxygen atom, asulfur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, anitrogen atom being optionally substituted by a C₁₋₆ alkyl group, aphenyl or a benzyl group; or a methylene group optionally substituted byone or two groups chosen from a C₁₋₆ alkyl group, a benzyl group, ahydroxy group, a C₁₋₄ alkoxy group, a C₃₋₆ cycloalkylmethyloxy, a C₁₋₂perhalogenated alkyl group, an amino group, an acetylamino group or aphenyl group; R1 represents a pyrimidine ring optionally substituted bya C₃₋₆ cycloalkyl group a C₁₋₄ alkyl group, a C₁₋₄ alkoxy group, abenzyl group or a halogen atom; when Y represents a covalent singlebond, a methylene group optionally substituted or a carbonyl group thenR2 represents a C₁₋₆ alkyl group optionally substituted by a C_(6,10)aryloxy or a C_(6,10) arylamino group; a C₃₋₆ cycloalkyl group, a C₁₋₄alkylthio group, a C₁₋₄ alkoxy group, a C₁₋₂ perhalogenated alkyl group,a C₁₋₃ halogenated alkyl group, a phenylthio group, a benzyl group, abenzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, anaphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, afuran ring or an imidazole ring; the benzyl group or the rings beingoptionally substituted by 1 to 4 substituents selected from a C₁₋₆ alkylgroup, a methylenedioxy group, a halogen atom, a C₁₋₂ perhalogenatedalkyl group, a C₁₋₃ halogenated alkyl group, a hydroxy group, a C₁₋₄alkoxy group, a nitro, a cyano, an amino, a C₁₋₅ monoalkylamino group, aC₂₋₁₀ dialkylamino group, a C₁₋₆ alkylcarbonylamino group, a C_(6,10)arylcarbonylamino group, a C₁₋₄ alkylsulfonyl group, C₁₋₄alkylsulfonyloxy group or a phenyl group; when Y represents anethenylene group, an ethynylene group, an oxygen atom, a sulfur atom, asulfonyl group, a sulfoxide group or a nitrogen atom being optionallysubstituted then R2 represents a C₁₋₆ alkyl group (optionallysubstituted by a C_(6,10) aryloxy or a C_(6,10) arylamino group), a C₃₋₆cycloalkyl group, a C₁₋₂ perhalogenated alkyl group, a C₁₋₃ halogenatedalkyl group, a benzyl group, a benzene ring, an indan ring, a5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring,a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; thebenzyl group or the rings being optionally substituted by 1 to 4substituents selected from a C₁₋₆ alkyl group, a methylenedioxy group, ahalogen atom, a C₁₋₂ perhalogenated alkyl group, a C₁₋₃ halogenatedalkyl group, a hydroxy group, a C₁₋₄ alkoxy group, a nitro, a cyano, anamino, a C₁₋₅ monoalkylamino group, a C₂₋₁₀ dialkylamino group, a C₁₋₆alkylcarbonylamino group, a C_(6,10) arylcarbonylamino group, a C₁₋₄alkylsulfonyl group, C₁₋₄ alkylsulfonyloxy group or a phenyl group; R3and R4 represent each independently a hydrogen atom, C₁₋₆ alkyl group, ahydroxy group, a C₁₋₄ alkoxy group or a halogen atom; R5 represents ahydrogen atom, a C₁₋₆ alkyl group or a halogen atom; when m equals 0, pequals 1, 2 or 3, when m equals 1, p equals 0, 1 or 2, when m equals 2,p equals 0 or 1; and n represents 0 to
 3. 2. The method according toclaim 1, wherein R1 represents an unsubstituted 4-pyrimidine ring. 3.The method according to claim 1, wherein the compound is selected fromthe group consisting of:9-(3-Phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl])-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Phenylsulfanyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(3-Hydroxy-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(1-Methyl-2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-1-methyl-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,tetrahydro-naphthalen-2-yl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Naphthalen-2-yl-2-oxo-ethy)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,-tetrahydro-naphthalen-2-yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-7,7,-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-2-phenyl-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Ethoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(2-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-(Benzo-[1,3]dioxol-5-yl)-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;4-[2-(3,3-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4,dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)ethyl]benzonitrile;9-[2-(4-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,6-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-naphthalen-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2-trifluoromethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-5-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-Indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;and9-[2-(5-Chloro-2,3-dihydro-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;or a pharmaceutically acceptable salt thereof.
 4. The method accordingto claim 1, wherein the compound is selected from the group consistingof:1-(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Oxo-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Hydroxy-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Biphenyl-4-yl-2-oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;2,2-Dimethyl-1-(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;2,2-Dimethyl-1-(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;and2,2-Dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)ethyl]-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;or a pharmaceutically acceptable salt thereof.
 5. The method accordingto claim 1, wherein the compound is selected from the group consistingof:9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(R)-Methoxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(R)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Bromo-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-naphthalen-2-yl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-(3-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)-1(S)-hydroxy-ethyl]-benzonitrile;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-(2-naphtalen-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2-oxo-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;and9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl]8-ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;or a pharmaceutically acceptable salt thereof.
 6. The method accordingto claim 1, wherein the disease is Alzheimer's disease.
 7. The methodaccording to claim 2, wherein the disease is Alzheimer's disease.
 8. Themethod according to claim 3, wherein the disease is Alzheimer's disease.9. The method according to claim 4, wherein the disease is Alzheimer'sdisease.
 10. The method according to claim 5, wherein the disease isAlzheimer's disease.
 11. The method according to claim 1, wherein thedisease is taupathies.
 12. The method according to claim 2, wherein thedisease is taupathies.
 13. The method according to claim 3, wherein thedisease is taupathies.
 14. The method according to claim 4, wherein thedisease is taupathies.
 15. The method according to claim 5, wherein thedisease is taupathies.
 16. A method of inhibiting the activity ofglycogen synthase kinase 3-beta (GSK3-β), which comprises administeringto a patient in need of said inhibition an effective amount of acompound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein: X represents two hydrogen atoms, a sulfur atom, an oxygen atomor a C₁₋₂ alkyl group and a hydrogen atom; Y represents a covalentsingle bond, an ethenylene group, an ethynylene group, an oxygen atom, asulfur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, anitrogen atom being optionally substituted by a C₁₋₆ alkyl group, aphenyl or a benzyl group; or a methylene group optionally substituted byone or two groups chosen from a C₁₋₆ alkyl group, a benzyl group, ahydroxy group, a C₁₋₄ alkoxy group, a C₃₋₆ cycloalkylmethyloxy, a C₁₋₂perhalogenated alkyl group, an amino group, an acetylamino group or aphenyl group; R1 represents a pyrimidine ring optionally substituted bya C₃₋₆ cycloalkyl group a C₁₋₄ alkyl group, a C₁₋₄ alkoxy group, abenzyl group or a halogen atom; when Y represents a covalent singlebond, a methylene group optionally substituted or a carbonyl group thenR2 represents a C₁₋₆ alkyl group optionally substituted by a C_(6,10)aryloxy or a C_(6,10) arylamino group; a C₃₋₆ cycloalkyl group, a C₁₋₄alkylthio group, a C₁₋₄ alkoxy group, a C₁₋₂ perhalogenated alkyl group,a C₁₋₃ halogenated alkyl group, a phenylthio group, a benzyl group, abenzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, anaphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, afuran ring or an imidazole ring; the benzyl group or the rings beingoptionally substituted by 1 to 4 substituents selected from a C₁₋₆ alkylgroup, a methylenedioxy group, a halogen atom, a C₁₋₂ perhalogenatedalkyl group, a C₁₋₃ halogenated alkyl group, a hydroxy group, a C₁₋₄alkoxy group, a nitro, a cyano, an amino, a C₁₋₅ monoalkylamino group, aC₂₋₁₀ dialkylamino group, a C₁₋₆ alkylcarbonylamino group, a C_(6,10)arylcarbonylamino group, a C₁₋₄ alkylsulfonyl group, C₁₋₄alkylsulfonyloxy group or a phenyl group; when Y represents anethenylene group, an ethynylene group, an oxygen atom, a sulfur atom, asulfonyl group, a sulfoxide group or a nitrogen atom being optionallysubstituted then R2 represents a C₁₋₆ alkyl group (optionallysubstituted by a C_(6,10) aryloxy or a C_(6,10) arylamino group), a C₃₋₆cycloalkyl group, a C₁₋₂ perhalogenated alkyl group, a C₁₋₃ halogenatedalkyl group, a benzyl group, a benzene ring, an indan ring, a5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring,a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; thebenzyl group or the rings being optionally substituted by 1 to 4substituents selected from a C₁₋₆ alkyl group, a methylenedioxy group, ahalogen atom, a C₁₋₂ perhalogenated alkyl group, a C₁₋₃ halogenatedalkyl group, a hydroxy group, a C₁₋₄ alkoxy group, a nitro, a cyano, anamino, a C₁₋₅ monoalkylamino group, a C₂₋₁₀ dialkylamino group, a C₁₋₆alkylcarbonylamino group, a C_(6,10) arylcarbonylamino group, a C₁₋₄alkylsulfonyl group, C₁₋₄ alkylsulfonyloxy group or a phenyl group; R3and R4 represent each independently a hydrogen atom, C₁₋₆ alkyl group, ahydroxy group, a C₁₋₄ alkoxy group or a halogen atom; R5 represents ahydrogen atom, a C₁₋₆ alkyl group or a halogen atom; when m equals 0, pequals 1, 2 or 3, when m equals 1, p equals 0, 1 or 2, when m equals 2,p equals 0 or 1; and n represents 0 to
 3. 17. The method according toclaim 16, wherein R1 represents an unsubstituted 4-pyrimidine ring. 18.The method according to claim 16, wherein the compound is selected fromthe group consisting of:9-(3-Phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl])-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Phenylsulfanyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(3-Hydroxy-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(1-Methyl-2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-1-methyl-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,tetrahydro-naphthalen-2-yl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Naphthalen-2-yl-2-oxo-ethy)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,-tetrahydro-naphthalen-2-yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-7,7,-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Hydroxy-2-phenyl-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Ethoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(2-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-(Benzo-[1,3]dioxol-5-yl)-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;4-[2-(3,3-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4,dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)ethyl]benzonitrile;9-[2-(4-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,6-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-9-(2-naphthalen-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2-trifluoromethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-5-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-Indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;and9-[2-(5-Chloro-2,3-dihydro-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;or a pharmaceutically acceptable salt thereof.
 19. The method accordingto claim 16, wherein the compound is selected from the group consistingof:1-(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Oxo-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Hydroxy-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-(2-Biphenyl-4-yl-2-oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;2,2-Dimethyl-1-(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;2,2-Dimethyl-1-(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;1-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;and2,2-Dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)ethyl]-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;or a pharmaceutically acceptable salt thereof.
 20. The method accordingto claim 16, wherein the compound is selected from the group consistingof:9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2-Methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(R)-Methoxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(R)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Bromo-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-naphthalen-2-yl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2(S)-Hydroxy-2-(3-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)-1(S)-hydroxy-ethyl]-benzonitrile;9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8,8-Dimethyl-9-(2-naphtalen-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-(2-Biphenyl-4-yl-2-oxo-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;and9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl]8-ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;or a pharmaceutically acceptable salt thereof.
 21. A compound which is9-[2-(5-chloro-2,3-dihydro-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-oneor a salt thereof.
 22. A compound which is9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-oneor a salt thereof.